The new Naviaux study is up! Metabolic features of CFS

[Remy]

@Who Me? is saying that is how the mass media reported it, as hibernation...not that it is how Naviaux described it.

In other words, the popular press is getting it wrong as usual.

 

[IrisRV]

Apparently I'm still not functioning on all cylinders. Looks like I need to go back into hibernation. Toodles! See you again in a few months.

 

[Who Me?]

Stop tagging or quoting me. @Remy. Thank you. I'm done with this.

 

[Issie]

https://ketosource.co.uk/exogenous-ketones-how-they-work/

Thanks. Interesting that on my last road trip, we were enroute with a guy in a very cool Pruvit truck. Being interested in learning, I told my hubby if we stopped with him I was going to talk to him and try to learn about it. We, a few hours later, stopped at the same gas station. I did talk to the guy and had a lengthy conversation and he gave me an KetoOS sample. WE have been exchanging emails and I'm learning. However, the MCT powder has milk proteins and corn and soy in it. I can't use any of that and reacted to the powder. From what I read most MCT powder is this way. It did however give me energy.

I had tried Butyrate already. It severely upsets my intestines. I only used a half bottle of it. Not sure why, unless there is some sort of milk protein associated with that too. I found a clean and cheaper source than the ones mentioned in that article.

I really like Damien blogs.
Issie

 

[Issie]

MEAction::
"Naviaux’s study in a nutshell states that the cells of ME patients are in a sort of protective hibernation"

Q&A with Dr. Naviaux:
"I wouldn’t use the term hibernation to describe chronic fatigue syndrome. Humans do not hibernate. Hibernation is just one of a handful of hypometabolic states that has been studied in different animals. There are many others that go by names like dauer, diapause, torpor, estivation, caloric restriction, etc. Many environmental stresses will trigger hypometabolism in humans. In our experience, the metabolic signature of dauer is more similar to CFS than some of the other hypometabolic states that have been studied."

mogaznews:
"Now, scientists have shown people with symptoms of the condition have a specific chemical signature in their blood."
"Lead researcher Robert Naviaux said something similar happens when animals dial down their metabolism to hibernate.
And that in CFS, the body may get stuck in this state, leading to chronic pain and disability."

telegraph:
"New research has revealed a chemical signature of the disease in the blood of those with ME. Scientists from the University of California claim it is similar to a state found in nematode worms called dauer, where the metabolism adjusts to a difficult environment by slowing down."
"This hibernation state enables existence, but not much more. ""

eurekaalert:
"...identify and assess targeted metabolites in blood plasma, have identified a characteristic chemical signature for the debilitating ailment and an unexpected underlying biology: It is similar to the state of dauer, and other hypometabolic syndromes like caloric restriction, diapause and hibernation."

I appreciated the highlights....makes it easier to gleen the meanings.

Issie

 

[Remy]

Apparently I'm still not functioning on all cylinders. Looks like I need to go back into hibernation. Toodles! See you again in a few months.

I am so confused now too! Don't go already...

 

[Remy]

Thanks. Interesting that on my last road trip, we were enroute with a guy in a very cool Pruvit truck. Being interested in learning, I told my hubby if we stopped with him I was going to talk to him and try to learn about it. We, a few hours later, stopped at the same gas station. I did talk to the guy and had a lengthy conversation and he gave me an KetoOS sample. WE have been exchanging emails and I'm learning. However, the MCT powder has milk proteins and corn and soy in it. I can't use any of that and reacted to the powder. From what I read most MCT powder is this way. It did however give me energy.

I had tried Butyrate already. It severely upsets my intestines. I only used a half bottle of it. Not sure why, unless there is some sort of milk protein associated with that too. I found a clean and cheaper source than the ones mentioned in that article.

I really like Damien blogs.
Issie

KetoCaNa is lactose and gluten free...it's not MCT but the calcium and sodium betahydroxybutyrate salts.

 

[Issie]

KetoCaNa is lactose and gluten free...it's not MCT but the calcium and sodium betahydroxybutyrate salts.

I'm not to use calcium. I saw one from a potassium source though. The one I tried is a potassium source, yet I still reacted. It also smells like rotten eggs. Horrible.
I'm good with MCT oil though.

 

[Issie]

I emailed the guy I met who sells Pruvit Keto OS and all their products. He said I could put his contact info on here in case anyone is interested in learning more about their products. He works with people to help them get the right product for them. His name is Ethan Godwin and his email is
emgodwin21@gmail.com I have his phone number too if anyone wants it you can message me. I think there is a way to become a distributor and get a discount. He can talk to you about that. They also have Facebook and some podcast. It's up and coming.

Issie

 

[ZeroGravitas]

Naviaux I think felt the media would jump on the hibernation idea and they have!

Wait, so was he (partly) baiting media interest with a catchy sounding concept? I initially thought you meant that he processed despite dreading misunderstanding. Seems to me that many/most other CFSers reading of the study via these articles are indeed coming away with the impression of a fuzzy-animal-type of 'hibernation' (jokingly or otherwise). Anyway...

I wrote about adenosine inducing a hibernation like syndrome a couple of years ago.

http://www.healthrising.org/forums/threads/role-of-adenosine-and-ada-in-mecfs.3860/

Ooh. I think I might also have caught that New Scientist article too (about squirrel brain adenosine receptor stimulation putting them (back) into hibernation). I certainly looked up adenosine after this other 2010 New Scientist article on how adenosine in the brain builds sleep pressure (and astrocytes appear to be the source). Anyway, that's quite a lot of interesting information! The years of expertise on here are quite intimidating, so please excuse me noobing in with my half arsed thinking now...

If we take Naviaux and these results at face value ("Plasma adenosine was decreased in females[...]"), then does this seem to contradict most of the previous thinking on adenosine? Like this tiny study in 2011 that found raised serum levels in CFSers. Remy's (and other's) raised test results, and theories (that I won't risk mincing via attempting to paraphrase). Also, the natural assumption that we must have too much as it's known to create tiredness. But then:

I thoughts most cfsers were tired but wired which doesnt make sense to me.

In many ways lowered adenosine, or lowered rate of production makes more sense here. One of our biggest certainties is mitochondria under-performing (either damaged, missing or inactivated). And if the primary source of adenosine accumulation is from our (diminished) "turnover (flux) of ATP and GTP" (Naviaux), then sleepiness inducing adenosine accumulation could well be muted and slowed, in line.

"[...] reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate" (Wikipedia) - so extra wired, like having caffeine blocking adenosine receptors (but from just less accumulating), but physically worn out in many other ways, particularly from the reduced ATP availability, for a start.

Also, adenosine seems to promote more efficient, more physically restorative, deep stage sleep (2005 paper) and more intense sleep in general (2012 paper), from comparing those with a common SNP (~10% population) that reduces the effect of the adenosine deaminase (ADA) gene (which break down adenosine).

If adenosine is broken down fairly rapidly in the blood (as I seem to be reading) then won't any variation in the activity of that degrading enzyme have a bigger effect on observed serum level than it's production rate (which can't vary tooo much, without the host dying?)? Isn't the issue, as with many quantities, where does it mostly come from and how much does actually cross over between areas? Would sampling the cerebrospinal fluid (CSF) give a different/more accurate/more relevant picture of adenosine build up? Or is even that going to be quite different to in-cell levels? Also, given the stated diurnal variation, won't the time of day a sample is taken also have a large effect? (Please excuse all the blathering, I imagine much like this must have already been discussed by better than me somewhere on one of the 'Rising forums...)

My personal anecdotal: I've never got into tea/coffee and caffeine pills/energy drink never seemed to do much of anything for me, so low adenosine would kinda make sense (with my gradual onset CFS). I've long had a 25h sleep cycle (currently ~26h) and imagine slower build-up of sleepiness might contribute to this. Also, from various sleep stage monitoring gadgets I seem to have more restless sleep first, too much REM and a whole load of deeper sleep right at the end of the 'night'. So maybe adenosine still building up during sleep, which would help explain it being extra hard for me to wake towards the end of sleep (cementing the lengthened, delayed cycle). But I've always been able to sleep a good long time (provided it's when my body wants to), so this topic has got me wondering if that saving grace is possibly down to a lucky, compensatory (genetic) variation, say also reducing my clearance rate of adenosine.

@Remy, what was your adenosine deaminase (ADA) SNP? Was it either of: the one mentioned in this different 2012 paper, causing stronger sleep pressure, depth and reduced alerness - Rs73598374 (which my 23andMe data shows a 'no call' on, frustratingly). Or even full on ADA deficiency (Wikipedia - 1 in 100k births). Also, sorry, I should probably have posted much of this in your thread on this topic.

EDIT: adenosine discussion continued here: http://www.healthrising.org/forums/threads/role-of-adenosine-and-ada-in-mecfs.3860/#post-23795

 

[Remy]

I'm good with MCT oil though.

MCT oil doesn't have as much of the C8 as you need for therapeutic ketosis levels. If you want to do an oil, I'd highly recommend Brain Octane or any other C8 oil over MCT or coconut.

 

[Francis Martin]

I’ve only looked briefly at this but they report “diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites”.

My understanding is that this is deliverable since the base cost is roughly £200 (US$230) per test – further detail below.

In terms of delivery, existing Government resources could be directed to confirming this test/testing samples from patients. Your Government currently uses this technique to test for antibiotics etc in food; so currently you rank behind chicken etc in their priorities.

I’m hoping that Vicky Whittemore [National Institutes of Health/National Institute of Neurological Disorders and Stroke] will fund a larger study to help to test this on a larger population. Also, fund research into what is turning on the switch [e.g. a dodgy sensor or an underlying infection] and how to address same. My confidence in the United Kingdom Government (who recently “contributed” PACE) and the European Union (who admittedly aren’t linked to PACE) is so low that my first call would be to Vicky. Please try to influence your Government including the UK/EU; however, my experience re UK/EU has not to date been positive.

Oh and well done to all involved. Not the simple answer I was hoping for i.e. here’s how you tell that you’ve got this and here’s how to correct it; but (on the face of it) a potential answer to the former and a step towards the latter.

Finally, ask your local politician (AKA “they work for you”!), including UK "PACE"/EU to deliver on this.

Further detail:
I’ve repeated this ad nauseam but the Government laboratories here in Northern Ireland get roughly £200 ($265 US) per LC-MS test i.e. for statutory food European Union residue testing (antibiotics etc). The technique used here i.e. metabolomics is a variation (of LC-MS/MS) which is more sensitive and as such is presumably more expensive (but presumably in the same ball park – perhaps twice the price per test).
In terms of capital cost, in relation to the Government laboratories here in Northern Ireland, I’ve previously seen figures in the region of £250,000 for an LC-MS/MS. I assume that these metabolomics instruments are in the same ball park possibly £400,000 ($530,000 US). At a very basic level my understanding is that they are an LC-MS/MS with a bit of fancy software i.e. to interpret the data collected (signal).
So testing of using this method (LC-MS/MS) is currently carried out by Government laboratories in Northern Ireland [(AFBI) - £200 ($265 US) per LC-MS test]; England, Scotland and Wales [Fera Science Limited], every other EU country and every significant food exporter (e.g. USA).

 

[Cort]

I’ve only looked briefly at this but they report “diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites”.

My understanding is that this is deliverable since the base cost is roughly £200 (US$230) per test – further detail below.

In terms of delivery, existing Government resources could be directed to confirming this test/testing samples from patients. Your Government currently uses this technique to test for antibiotics etc in food; so currently you rank behind chicken etc in their priorities.

I’m hoping that Vicky Whittemore [National Institutes of Health/National Institute of Neurological Disorders and Stroke] will fund a larger study to help to test this on a larger population. Also, fund research into what is turning on the switch [e.g. a dodgy sensor or an underlying infection] and how to address same. My confidence in the United Kingdom Government (who recently “contributed” PACE) and the European Union (who admittedly aren’t linked to PACE) is so low that my first call would be to Vicky. Please try to influence your Government including the UK/EU; however, my experience re UK/EU has not to date been positive.

Oh and well done to all involved. Not the simple answer I was hoping for i.e. here’s how you tell that you’ve got this and here’s how to correct it; but (on the face of it) a potential answer to the former and a step towards the latter.

Finally, ask your local politician (AKA “they work for you”!), including UK "PACE"/EU to deliver on this.

Further detail:
I’ve repeated this ad nauseam but the Government laboratories here in Northern Ireland get roughly £200 ($265 US) per LC-MS test i.e. for statutory food European Union residue testing (antibiotics etc). The technique used here i.e. metabolomics is a variation (of LC-MS/MS) which is more sensitive and as such is presumably more expensive (but presumably in the same ball park – perhaps twice the price per test).
In terms of capital cost, in relation to the Government laboratories here in Northern Ireland, I’ve previously seen figures in the region of £250,000 for an LC-MS/MS. I assume that these metabolomics instruments are in the same ball park possibly £400,000 ($530,000 US). At a very basic level my understanding is that they are an LC-MS/MS with a bit of fancy software i.e. to interpret the data collected (signal).
So testing of using this method (LC-MS/MS) is currently carried out by Government laboratories in Northern Ireland [(AFBI) - £200 ($265 US) per LC-MS test]; England, Scotland and Wales [Fera Science Limited], every other EU country and every significant food exporter (e.g. USA).

I know that Whittemore has met with Ron Davis and supports his work. I hope we can find a way to get a big metabolomics grant on ME/CFS. Maureen Hanson recently stated that she is going to try and get one. Stay tuned for some news on testing for metabolomics

 

[Francis Martin]

Thanks Cort.
Did I pick up that Maureen Hanson also has data re possible diagnostic metabolites (seemed to recall this from the Invest in ME conference in June 2016) and if so any news of it being published? I imagine that there are a few folks looking back at their old data to see if it correlates with this (Naviaux) study.
One thing I forgot to emphasise, this is a blood test i.e. an accessible sample; proteomics studies relied on cerebral spinal fluid i.e. not an accessible sample.